Effects of an extreme natural disaster on immunity and aging

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PROJECT SUMMARY Extreme adverse environmental events, such as major hurricanes, are associated with increased incidence and severity of a myriad of health problems. Intriguingly, many of these ailments are also more prevalent in older individuals–hinting that adversity and aging affect the immune system in similar ways. Together, this suggests that adverse experiences may accelerate immune system aging. Disruptions to immune gene regulation can persist for many years and are expected to be a particularly salient mechanism by which extreme natural disasters drive aging-associated health declines. Additionally, individuals exhibit extensive heterogeneity in their responses to adversity, and factors such as social adversity (i.e., socioeconomic status, social integration), chronological age, and sex have been linked to differential health outcomes following disaster. However, most studies to date have focused on opportunistically collected samples without baseline data, and none have investigated whether gene expression and DNA methylation are accelerated by extreme hurricanes and how social experiences, chronological age, and sex affect multiple domains of immune gene regulation and aging. The goal of the proposed research is to address these gaps by taking advantage of an unparalleled sample of rhesus macaques (Macaca mulatta) from the island of Cayo Santiago that recently experienced Hurricane Maria. Macaques are a well-established animal model for translational human aging research because they share many genetic, social, and immunological features with humans. Peripheral whole blood samples for RNA were collected annually from representative samples of juvenile and adult male and female macaques for three years immediately prior to (2014-2016) and one year after (2018) Hurricane Maria. Blood samples for DNA were collected from 2010-2016 and in 2018. I will use this unique opportunity to investigate the effects of Hurricane Maria and its aftermath on gene regulation and biological aging of the peripheral immune system by quantifying changes to and aging of peripheral gene expression and DNA methylation. This aim will extend studies of adversity and immune gene regulation to extreme natural disaster and quantify immune system aging at multiple levels. Second, I will measure the effects of social adversity, chronological age, and sex on peripheral gene expression and DNA methylation and pace of aging. This aim will provide insight into how these factors influence the heterogeneity in immune responses and modulate immune aging following a major hurricane. Together, these studies will provide insight into how extreme natural disasters impact immune gene regulation and how several pertinent social and demographic factors shape these responses. The proposed work will add to the growing body of research on natural disaster and immune gene regulatory disruptions and introduce the integration of socio-demographic data to evaluate heterogeneity in multiple domains of immune aging. This work represents an incredible training opportunity for the fellow and will provide valuable insight into how extreme disasters drive poor health outcomes and who is most vulnerable to these negative effects.